Section VIII:

Review Types/Process

WPP #: VIII-5

Title 5:

Review of Modification to Research

Effective Date:

09-24-14

Revision History:

06-20-00; 08-29-00; 06-07-04; 06-21-06; 02-05-07; 9-30-07; 09-1-09; 03-01-11; 05-13-14

Policy Statement

Federal regulations require that modifications to research activities not be initiated without prior IRB review and approval except when necessary to eliminate apparent immediate hazards to subjects (in which case the investigator must promptly report the modification to the IRB).

Description and Procedures

Investigators must report planned modifications in the conduct of research and receive IRB approval PRIOR to implementing these changes, as specified below depending on the review category of the research. At the time a study receives IRB approval principal investigators receive a letter of approval that outlines the requirement to submit any changes in their research project to the IRB for prior review and approval. Modifications that were unplanned and involved deviations from the protocol in order to minimize or eliminate a serious hazard are unanticipated problems that involve risk to subjects or others. See WPP #VIII-7: Required Reporting of Unanticipated Problems Involving Risk or Harm to Subjects or Others.

Modifications include, but are not limited to, procedural changes to a protocol, requesting additional subjects beyond the approved number, changes in protocol or investigational drug brochure, and any changes in informed consent materials or advertisements.

  1. Modifications to Exempt Studies

    The following changes to the protocol must be submitted to the IRB panel for review and approval before the changes are instituted. Changes that do not meet these criteria do not have to be submitted to the IRB. If there is a question about whether a change must be sent to the IRB please contact ORSP for clarification.

    1. Change in principal investigator
    2. Any change that increases the risk to the participant
    3. Addition of children, wards of the state, or prisoner participants
    4. Changes in survey or interview questions (addition or deletion of questions or wording) that change the level of risk or adds questions related to sexual activity, abuse, past or present illicit drug use, illegal activities, questions reasonably expected to provoke psychological anxiety, or would make participants vulnerable, or subject them to financial, psychological or medical risk
    5. Changes that change the category of exemption or add additional exemption categories
    6. Changes that add procedures or activities not covered by the exempt category or categories under which the study was originally determined to be exempt
    7. Changes requiring additional participant identifiers that could impact the exempt category or determination
    8. Change in inclusion dates for retrospective record reviews if the new date is after the original approval date for the exempt study. (ex: The approval date for the study is 9/24/10 and the original inclusion dates were 01/01/08-06/30/10. This could be changed to 01/01/06 to 09/24/10 but not to end on 09/25/10 or later.)
    9. Addition of a new recruitment strategy
  2. Types of Modifications to Expedited and Full Review Studies:

    Modifications fall into one of two categories: minor modifications or major modifications. The principal investigator makes the initial assessment of minor vs. major modification and submits the proposed change to the IRB accordingly. Final determination of the review level rests with the IRB.

    1. Minor Modifications:
      1. Involve no added risk beyond minimal risk; and
      2. Make no substantive change to study design.
        Final determination of changes that qualify as minor is made by the IRB.
    2. Major Modifications are modifications that are not minor. Note that a major modification to an expedited review protocol may increase the risk to greater than minimal risk and thus changes the review status to full board.
  3. IRB Evaluation of Type of Modification:
    1. Examples of modifications that may be minor:
      1. Changes to contact information in study documents
      2. Correction of typographic and grammatical errors that do not change the meaning of the protocol.
      3. Modified wording to clarify the original intent of the protocol that does not change its meaning (e.g., “Store drug at 4 degrees” to “Store drug in a refrigerator at 4 degrees C.” “WBC<2400” to “WBC<2400 (either manual or automated counting is acceptable.”).
      4. Personnel changes that do not alter the competence of the research team to conduct the research.
      5. Revisions to study instruments that do not impact the intent or risk level (Note: addition of questions pertaining to drug / alcohol use or psychological wellbeing is likely to change risk).
      6. Changes in research procedures that have no more than a minor risk of harm, such as changes in the amount and frequency of blood draws (remaining within expedited criteria levels), addition of a clinic visit that involves no new procedures, or addition of a questionnaire that does not introduce new subject matter.
      7. Adding new recruitment materials or modifications to existing recruitment materials.
    2. Examples of modifications that may or may not be major:
      1. Changes to study design or methodology
      2. Extending the time period of the study for follow-up depending on what procedures will be done in follow-up.
      3. Adding a research site.
      4. Change of PI - This may be considered minor (and thereby can be reviewed as expedited) if the following criteria apply:
        1. the individual must have known VCU research experience
        2. the individual is well-qualified to carry out the research in the designated research role, and
        3. the individual has other similar types of research projects with the IRB. If the criteria do not apply, a change in PI must be reviewed by the full board.
        Note: If FDA-regulated research, a proposed change in PI not meeting the above criteria should be verified by the Office of Research Subjects Protection for eligibility to serve as a PI via the FDA Bioresearch Monitoring page. (Under “Compliance Lists” check the Disbarment and Disqualified/Restricted/Assurance Lists for the proposed PI’s name.)
    3. Examples of modifications that are likely major: (If, after consideration by the Chair and/or primary reviewer, the minor modification criteria above apply, the review may be carried out as expedited).
      1. Significant changes in study design.
      2. Changing the treatment or intervention.
      3. Increasing /decreasing the drug dosage or changing the frequency of drug administration.
      4. Changes in inclusion/exclusion criteria.
      5. New risk information and/or changes in risk to participants.
  4. Expedited Review of Minor and Major Modifications to Studies Originally Reviewed as Expedited:

    Proposed modifications to research previously approved via expedited review during the period for which approval has been granted may be reviewed by expedited review unless the change results in the research activity no longer meeting the conditions for expedited review. In this case, the modification request will be referred for full board action.

  5. Full Board Review of Modifications:

    Proposed modifications to research originally reviewed via full board review are reviewed via full board review unless found to be minor, as defined above.

    1. All materials necessary to review modifications are distributed to reviewers and attending IRB members in sufficient time prior to the meeting to allow for adequate review. This includes all revised materials, including but not limited to the full protocol, consent document, recruitment materials and investigator’s brochure/drug labeling.
    2. The IRB reviews the modification to determine whether the criteria for approval are still met when the modifications affect one or more criterion.
  6. Review of Minor Modifications to Research Previously Approved by the Full Board:
    1. Federal guidelines state that "An IRB may use the expedited review procedure to review minor changes in previously approved research during the period (of one year or less) for which approval is authorized.” [45 CFR 46.110(b)(2)].
    2. The expedited review procedure allows the IRB Chairperson and/or an assigned member of the IRB to review the modification and determine approval. A modification cannot be disapproved by expedited review; however, the Chairperson or the IRB member may recommend that the modification be reviewed by the full IRB. Thus, expedited procedures may be used for minor modifications.
    3. If there is any protocol-related information requiring clarification, the expedited reviewer will contact the principal investigator (or student/trainee conducting the activity) directly.
    4. All members of the IRB will be informed of modifications to study protocols approved by the expedited review procedures as part of the IRB agenda, agenda attachment, and minutes (as appropriate).
    5. Final review comments by the expedited reviewer are documented in writing.
  7. Changes to Eliminate Apparent Immediate Hazards to Participants
    1. If deemed necessary by the investigator, changes in approved research that are initiated without IRB approval in order to eliminate apparent immediate hazards to the participant must:
      1. Be promptly (no longer than within 30 days) reported to the IRB.
      2. Be reviewed by the IRB to determine whether each change was consistent with ensuring the participants’ continued welfare.

References

45 CFR 46.110(b)(2)